{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T01:45:54Z","timestamp":1782956754803,"version":"3.54.5"},"reference-count":53,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Systemic sclerosis (SSc) is a rare but severe autoimmune disease characterized by immune dysregulation, fibrosis, and vasculopathy. Although previous studies have highlighted the presence of functional autoantibodies targeting the angiotensin II receptor type 1 (AT\n                      <jats:sub>1<\/jats:sub>\n                      ) and endothelin\u20101 type A receptor (ET\n                      <jats:sub>A<\/jats:sub>\n                      R), leading to autoantibody\u2010mediated receptor stimulation and subsequent activation of endothelial cells (ECs), a comprehensive understanding of the direct interaction between these autoantibodies and their receptors is currently lacking. Moreover, existing data confirming the presence of these autoantibodies in SSc often rely on similar methodologies and assays. Our aim was to replicate previous findings and to investigate the functional effects of IgG derived from patients with SSc (SSc IgG) on AT\n                      <jats:sub>1<\/jats:sub>\n                      and ET\n                      <jats:sub>A<\/jats:sub>\n                      R signaling, the downstream EC response, and the presence of AT\n                      <jats:sub>1<\/jats:sub>\n                      \u2010binding autoantibodies in circulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Quantitative polymerase chain reaction and cytokine enzyme\u2010linked immunosorbent assay, alongside a real\u2010time cell analyzer, were used to assess receptor\u2010specific functional characteristics of purified SSc IgG (n = 18). Additionally, a novel protein capture assay using solubilized epitope\u2010tagged AT\n                      <jats:sub>1<\/jats:sub>\n                      was developed to detect AT\n                      <jats:sub>1<\/jats:sub>\n                      \u2010binding autoantibodies in plasma samples from patients with SSc (n = 28) and healthy donors (n = 14).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No evidence for EC activation in an AT\n                      <jats:sub>1<\/jats:sub>\n                      \u2010 or ET\n                      <jats:sub>A<\/jats:sub>\n                      R\u2010dependent manner was revealed. Furthermore, stimulation with SSc IgG did not induce receptor activation or alter G protein\u2010coupled receptor signaling on agonist stimulation in a model with receptor overexpression. Lastly, no AT\n                      <jats:sub>1<\/jats:sub>\n                      \u2010binding autoantibodies were detected in plasma samples from patients with SSc when using epitope\u2010tagged solubilized AT\n                      <jats:sub>1<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Overall, our study did not provide evidence to support the presence of AT\n                      <jats:sub>1<\/jats:sub>\n                      \u2010 or ET\n                      <jats:sub>A<\/jats:sub>\n                      R\u2010activating autoantibodies in purified SSc IgG or AT\n                      <jats:sub>1<\/jats:sub>\n                      \u2010binding autoantibodies in the circulation of patients with SSc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.43099","type":"journal-article","created":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T20:54:04Z","timestamp":1735160044000},"page":"901-913","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Absence of Functional Autoantibodies Targeting Angiotensin\n                    <scp>II<\/scp>\n                    Receptor Type 1 and Endothelin\u20101 Type A Receptor in Circulation and Purified\n                    <scp>IgG<\/scp>\n                    From Patients With Systemic Sclerosis"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5619-4508","authenticated-orcid":false,"given":"Wieke M.","family":"van Oostveen","sequence":"first","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2437-6016","authenticated-orcid":false,"given":"Eva M.","family":"Hoekstra","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. W. Nivine","family":"Levarht","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilana B.","family":"Kotliar","sequence":"additional","affiliation":[{"name":"The Rockefeller University and Tri\u2010Institutional PhD Program in Chemical Biology  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"Sakmar","sequence":"additional","affiliation":[{"name":"The Rockefeller University  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 E. M.","family":"Toes","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeska K.","family":"de Vries\u2010Bouwstra","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura H.","family":"Heitman","sequence":"additional","affiliation":[{"name":"Leiden University and Oncode Institute  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9020-1591","authenticated-orcid":false,"given":"Cynthia M.","family":"Fehres","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The 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